Fast startup ion chromatography system and methods

ABSTRACT

Systems and methods for inhibiting translocation of ions across ion exchange barriers include an eluent generator having an ion source reservoir with a first electrode, an eluent generation chamber with a second electrode, an ion exchange barrier disposed therebetween, and means for reversing the polarity of a voltage or current applied across the first and second electrodes. A first polarity voltage or current applied across the electrodes generates an electric field that promotes translocation of eluent counter ions from the reservoir across the barrier, where the counter ions combine with eluent ions electrolytically generated in the chamber. By reversing the polarity of the voltage or current across the electrodes, the resulting electric field inhibits translocation of counter ions across the barrier from the reservoir into the chamber. Reverse voltage or current bias reduces counter ion concentration in the resting chamber to prevent exhaustion of ion suppressor capacity during start up.

CROSS-REFERENCE TO RELATED APPLICATIONS

Not applicable.

BACKGROUND OF THE INVENTION 1. Technical Field

The present disclosure relates generally to systems and methods forinhibiting translocation of eluent and/or ions across an ion exchangebarrier, particularly in an eluent generation device for generating ahigh purity acid or base, particularly for use as a chromatographyeluent, and to a method of using the apparatus.

2. Relevant Technology

In liquid chromatography systems, a sample containing a number ofcomponents to be separated is directed through a chromatographyseparator, such as an ion exchange resin bed, typically disposed in acolumn or cartridge. The sample components are separated via elutionfrom the bed by means of an eluent, such as an ionic solution. Oneeffective form of liquid chromatography is referred to as ionchromatography. In this technique, ion analytes to be detected in asample solution are bound to the separator, washed, eluted using aneluent, often containing an acid or base, directed to a suppressor, anddetected, typically by an electrical conductivity detector. In thesuppressor, the electrical conductivity of the electrolyte eluent issuppressed but not that of the separated ion analytes, so the latter maybe detected by the conductivity detector. This technique is described indetail in U.S. Pat. Nos. 4,999,098, 6,077,434, and 6,328,885, theentirety of each of which is incorporated herein by specific reference.

The eluent for ion chromatography can be generated with an eluentgenerator, which can generate high purity eluents at predeterminedconcentrations. A controlled and precise amount of an electric currentcan be applied to electrolyze water to generate hydroxide and hydroniumions. Eluent generation is desirable because it circumvents the need tomanually prepare eluents from concentrated acids and bases. Often themanual preparation of eluents is both labor intensive and involvesworking with hazardous chemicals. Eluent generators can be configured sothat the only user added reagent is deionized water, which is pumpedinto the eluent generation cartridge. Furthermore, since the instrumentpump seals and pistons only come in contact with deionized water insteadof acids and bases which can salt out and come out of solution, overallpump maintenance is significantly reduced. It is also worthwhile to notethat since eluent generators create eluent immediately before use in anion chromatography system, this reduces the likelihood of contaminantssuch as carbon dioxide from ambient air from contaminating the eluent.An example of an eluent generator is described in U.S. Pat. No.6,225,129, the entirety of which is incorporated herein by specificreference. Such techniques are applicable to chromatography,specifically ion chromatography, as well as other analyticalapplications using acid or base such as flow injection analysis and thelike.

One drawback to existing analyte detection systems is that eluentgenerators (e.g. a component of an ion exchange chromatography system)and related systems, under certain circumstances, may require asubstantial amount of startup and/or equilibration time before analyteions can be processed (e.g., injected) for identification and/orquantification. Such startup and/or equilibration time results in aninefficient use of an analyst's time. Accordingly, it would bebeneficial to provide systems and methods for reducing the startupand/or equilibration time of eluent generators and related systems sothat an analyst can process more samples per day.

BRIEF SUMMARY Overview and Technical Problem

Eluent generation systems include an eluent generator cartridge havingan ion source reservoir containing an ion source (e.g., a fluid ionssource or solution). The ion source and/or reservoir contains eluentcounter ions, usually at a high concentration (e.g., typically about 2-4N). The eluent generator cartridge also includes an eluent generationchamber and at least an ion exchange barrier disposed between the ionsource reservoir and the eluent generation chamber. The ion exchangebarrier can substantially prevent liquid flow, and generally allowspassage of one ion type (i.e., positive or negative, but not both)through the ion exchange barrier while providing an ion transport bridgethat permits the transport of the eluent counter ions from the sourcereservoir to the generator chamber. Accordingly, the eluent generationchamber is isolated or fluidly separated from the ion source reservoirby the ion exchange barrier. The system also includes a source electrodein physical and/or electrical communication with the ion source disposedin the ion source reservoir and a generator electrode in physical and/orelectrical communication with the eluent generation chamber and/or aliquid (e.g., water, such as deionized water) disposed therein. In someembodiments, the electrode(s) may be made of perforated platinum.

During operation of a cation hydroxide eluent generation, for example,the liquid stream flows through the eluent generation chamber so as tobe in communication with the generator electrode. The ion sourcereservoir can contain a high concentration hydroxide solution, such asKOH, NaOH, LiOH, etc. In response to a voltage having a first polarityapplied across the electrodes (or current or charge flow in a firstdirection between the electrodes), the generator electrode can produceeluent ions (e.g., OH⁻) in the eluent generation chamber through awater-splitting reaction. Similarly, the source electrode can producehydronium (i.e., H₃O⁺) or H⁺ in the ion source reservoir throughwater-splitting reaction in response to the first polarity voltage (orfirst direction current or charge flow). The produced hydronium reactswith hydroxide present in the reservoir to produce water. This producesan excess charge since there is now an excess of cation relative toanion, which results in the ejection of the excess cation. Thus,production of an electric field between the ion source reservoir and theeluent generation chamber drives (or promotes) transport of eluentcounter ions (e.g., K⁺, Na⁺, Li⁺, etc.) from the source reservoir,across the membrane, and into the generation chamber, where the counterions combine with the produced eluent ions (e.g., OH⁻) to form eluent(e.g., KOH, NaOH, LiOH, etc.). The generated eluent is carried by thestream flow out of the cartridge, through one or more further processingcomponents (e.g., a trap column, such as a continuously-regenerated trapcolumn (CR-TC), a degasser, a backpressure control element, such as acoil, an injector, a guard column, etc.) and, ultimately, into theanalytical chromatography column to elute the retained analyte moleculesof interest.

During downtime, however, when the system is in passive or shutdownmode, or is turned off, neither the stream flow nor the external appliedvoltage (or current) is operational. It is worthwhile to note that thedowntime mode represents a time period where the ion chromatographysystem is powered down at the end of a work shift of the analyst or thatthere are no plans to analyze additional samples for a prolonged periodof time (e.g. a weekend). In this downtime mode, deionized water is notbeing pumped through the eluent generation chamber. Applicant believesthat many analytical laboratories prefer to power down ionchromatography systems when not analyzing samples to reduce costs forelectricity. In an embodiment, powering down ion chromatography systemscan include not applying electricity to the pump, suppressor, anddetector. During this downtime, an ion exchange membrane can permiteluent in the ion source reservoir to passively diffuse from thereservoir into the generation chamber (e.g., at a passive rate ofdiffusion towards equilibrium, due to the concentration differential).The eluent can have a pair of ions (e.g., K⁺OH⁻) that has a net neutralcharge and can slowly diffuse through an ion exchange membrane based ona concentration gradient.

Over an extended period of time (e.g., hours, days, weeks, etc.), wherethere is no fluid flow through the generation chamber, the concentrationof ions in the resting chamber can be or become substantially similar tothe concentration of ions in the reservoir. For instance, in somesystems (or cartridges), the volume ratio of reservoir-to-chamber issubstantial enough to bring the concentration of ions in the restingchamber (or stationary liquid, such as deionized water, disposedtherein) to about 2-4 N. Without being bound to any theory, the passivediffusion stops once the concentration is equal in both the sourcereservoir and generation chamber. Passive diffusion can causesignificant amounts of leakage of ions from the ion source chamber overlonger periods of time where the liquid in the generation chamber isquiescent. In contrast to passive diffusion, and without being bound toany theory, an electric field generated between the first and secondelectrodes can cause ions of one charge to be actively transportedthrough an ion exchange membrane and in some instances at a rate muchfaster than passive diffusion. The effects of passive diffusiongenerally increase with decreasing flow rate and when the liquid in thegeneration chamber is quiescent.

Upon restarting the system by establishing flow, a concentrated ion plug(or slug)—i.e., the stationary liquid with high ion concentration—flowsout of the generation chamber and/or cartridge and through the furtherprocessing component(s) and/or chromatography column. Transit of thehigh concentration plug through the system causes multiple issues withthe ion chromatograph. For example, the large concentration gradientmust be swept or flushed from the system plumbing components (e.g.,lines, valves, etc.) before the system can be operated at optimal levelsto process (e.g., injected) analyte ions for identification and/orquantification. Sweeping or flushing the plumbing components of thesystem can be time-consuming and require additional monitoring byoperation personnel or users. The issue is worse when the flow rate ofthe system is low. Alternatively, or in addition, the column may requireadditional equilibration time to reach a steady, low, baseline readingand/or column equilibration may be affected in other ways.Alternatively, or in addition, the capacity of the ion suppressor (inline downstream of the eluent generator) can be exhausted by the highion concentration plug, requiring additional time for regeneration ofthe suppressor. Overall, the impact of the high concentration plugincludes added system equilibration time needed for optimalchromatographic operation during analyte ion processing. This additionaltime translates into additional labor and operation costs.

Solution to Technical Problem

The present disclosure solves one or more of the foregoing issues byproviding a solution to passive eluent and/or ion diffusion during timesof the eluent generator resting when there is no external appliedcurrent or voltage between the electrodes. Some embodiments can includesystems and methods for inhibiting accumulation of species ions in aneluent generation chamber. In particular, the present disclosure solvesthe issue of extended startup and/or equilibration time in ionchromatography (IC) systems (e.g., an ion exchange chromatographysystem) by applying a reversed bias voltage (or current) on or acrossthe eluent generator (EG) component (or cartridge) during a downtime orin a downtime or idle system mode(s). The reverse voltage bias (orcurrent) generates an electric field that inhibits translocation ofeluent (e.g., KOH) and/or eluent counter ions (e.g., K⁺) across the ionexchange membrane from the source reservoir to the generation chamber,preferably thereby at least partially inhibiting accumulation of theeluent counter ions and/or eluent in a generation chamber.

In at least one embodiment of the present disclosure, a method ofinhibiting translocation and/or accumulation of eluent and/or eluentcounter ions comprises applying a voltage across a first electrode and asecond electrode, the voltage having a second (or reversed) polarity,the first and second electrodes being disposed on first and second sidesof an ion exchange membrane, respectively, the applied voltage with thesecond polarity electrolytically generating hydronium ions at the secondside of the ion exchange membrane, the electric field generated betweenthe first and second electrodes inhibiting translocation of the eluentand/or eluent counter ions through (or across) the ion exchange membranefrom the first side to the second side, preferably thereby inhibitingaccumulation of eluent and/or eluent counter ions at the second side.

In this reversed bias mode, the eluent generator electrode forms ions(either hydronium or hydroxide from the water splitting reaction) thatcan migrate towards the reservoir electrode (e.g., because of thepotential difference across the membrane and/or electrostaticattraction). In an embodiment, cation hydroxide can passively diffusefrom the electrolyte reservoir to the generation chamber and hydroxidecan be neutralized by the electrolytically generated hydronium ion inthe generation chamber. In addition, potassium and/or hydronium ion canbe driven from the generation chamber to the electrolyte reservoir.

The system can also be run in an active (or standard) mode, as known inthe art, by applying a voltage across a first electrode and a secondelectrode, the voltage having a first polarity so that electrolyticallygenerated eluent can be used in a chromatographic analysis of a samplecontaining analyte. The first polarity voltage can generate an electricfield that promotes translocation of the eluent counter ions across theion exchange membrane from the first side to the second side. Someembodiments can include selectively reversing the polarity of thevoltage from the first polarity to the second polarity, selectivelyreversing the polarity of the voltage from the second polarity to thefirst polarity.

Certain embodiments can include a system for inhibiting translocationand/or accumulation of ions across an ion exchange membrane. The systemcan include a first electrode in electrical communication with an ionsource disposed in an ion source reservoir, a second electrode inelectrical communication with an eluent generation chamber, an ionexchange membrane disposed between the ion source reservoir and theeluent generation chamber, and means for reversing the polarity of avoltage across the first and second electrodes. An aqueous fluid, suchas deionized water, can be disposed in or flowing through the eluentgeneration chamber, such that when the voltage is applied across thefirst and second electrodes with a first polarity, the subsequentlygenerated electric field inhibits eluent counter ions from translocatingacross the ion exchange membrane into the liquid.

In some embodiments, the reversed bias potential can be applied toreduce translocation of eluent counter ions across an ion exchangemembrane, from the reservoir to the generation chamber, during storage,downtime, or non-operation times. Ion transport inhibition can preventor inhibit the formation of a high concentration plug of ions from theion source reservoir in the resting generation chamber. Accordingly,startup and/or equilibration time need not include a substantial amountof additional flushing, sweeping, or suppressor regeneration time (priorto injection of analyte ions). The net effect is a faster startup timeof the system without the issues associated with a high concentrationplug.

Certain embodiments include a method of determining an optimal reversebias mode voltage or current for achieving reduced startup time. Themethod can include passing (e.g., pumping) an aqueous fluid or liquid(e.g., deionized water) through the generation chamber while the voltageor current is applied in the reversed bias mode and monitoring theoutput from the generation chamber (e.g., using a conductivitydetector). In some embodiments, the voltage or current is adjusted oroptimized until a lowest possible value of conductivity is obtained orobserved from the liquid pumped out of the generation chamber. Withoutbeing bound to any theory, at the lowest conductivity value, thetransport of ions from the reservoir into the eluent generation chamberis at a minimum (or minimal). The voltage or current values associatedwith the lowest conductivity can be used in one or more storage methods,as described herein. Cartridges stored at the minimal conductivityvoltage or current value(s) overnight or over several days (as indicatedon the system) can exhibit excellent performance and/or rapid startupand/or equilibration times when normal operation of the system isresumed. For instance, analyte ions can be injected immediatelyfollowing system startup or within a substantially shortenedequilibration period relative to existing systems and methods. Theshortened time between startup and analyte ion injection can be lessthan typical equilibration times.

Additional features and advantages of the disclosure will be set forthin the description which follows, and in part will be obvious from thedescription, or may be learned by the practice of the disclosure. Thefeatures and advantages of the disclosure may be realized and obtainedby means of the instruments and combinations particularly pointed out inthe appended claims. These and other features of the present disclosurewill become more fully apparent from the following description andappended claims, or may be learned by the practice of the disclosure asset forth hereinafter.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to describe the manner in which the above-recited and otheradvantages and features of the invention can be obtained, or to furtherclarify the above and other advantages and features of the presentdisclosure, a more particular description of the disclosure brieflydescribed above will be rendered by reference to specificimplementations and/or embodiments thereof which are illustrated in theappended drawings.

Furthermore, it will be readily appreciated that the components of theillustrative embodiments, as generally described and illustrated in thefigures herein, could be arranged and designed in a wide variety ofdifferent configurations, and that components within some figures areinterchangeable with, or may supplement, features and componentsillustrated in other figures. Accordingly, understanding that thedrawings depict only typical implementations and/or embodiments of thedisclosure and are not, therefore, to be considered to be limiting ofits scope, the embodiments will be described and explained withadditional specificity and detail through the use of the accompanyingdrawings in which:

FIG. 1 illustrates a general chromatography system suitable for use withan embodiment of the present disclosure;

FIG. 2A illustrates an eluent generation systems or module in accordancewith an embodiment of the present disclosure;

FIG. 2B illustrates an eluent generation systems or module in accordancewith another embodiment of the present disclosure;

FIG. 3A illustrates a schematic flow diagram for an eluent generationsystems or module in accordance with an embodiment of the presentdisclosure;

FIG. 3B illustrates a schematic flow diagram for an eluent generationsystems or module in accordance with another embodiment of the presentdisclosure;

FIG. 3C illustrates a schematic flow diagram for an eluent generationsystems or module in accordance with yet another embodiment of thepresent disclosure;

FIG. 4 illustrates exemplary performance of a standard eluent generator;

FIG. 5 illustrates exemplary performance of an eluent generator systemin accordance with an embodiment of the present disclosure;

FIG. 6 illustrates exemplary performance of an eluent generator systemin accordance with another embodiment of the present disclosure;

FIG. 7 illustrates exemplary performance of an eluent generator systemin accordance with yet another embodiment of the present disclosure; and

FIG. 8 illustrates exemplary performance of an eluent generator systemin accordance with still another embodiment of the present disclosure.

DETAILED DESCRIPTION

Before describing the present disclosure in detail, it is to beunderstood that this disclosure is not limited to the specificparameters of the particularly exemplified systems, methods, apparatus,assemblies, products, processes, and/or kits, which may, of course,vary. It is also to be understood that much, if not all of theterminology used herein is only for the purpose of describing particularembodiments of the present disclosure, and is not necessarily intendedto limit the scope of the disclosure in any particular manner. Thus,while the present disclosure will be described in detail with referenceto specific configurations, embodiments, and/or implementations thereof,the descriptions are illustrative only and are not to be construed aslimiting the scope of the claimed invention.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which the present disclosure pertains. While a number ofmethods and materials similar or equivalent to those described hereincan be used in the practice of the present disclosure, only certainexemplary materials and methods are described herein.

Various aspects of the present disclosure, including systems, methods,and/or products may be illustrated with reference to one or moreembodiments or implementations, which are exemplary in nature. As usedherein, the terms “embodiment” and “implementation” mean “serving as anexample, instance, or illustration,” and should not necessarily beconstrued as preferred or advantageous over other aspects disclosedherein. In addition, reference to an “implementation” of the presentdisclosure or invention includes a specific reference to one or moreembodiments thereof, and vice versa, and is intended to provideillustrative examples without limiting the scope of the invention, whichis indicated by the appended claims rather than by the descriptionthereof.

As used throughout this application the words “can” and “may” are usedin a permissive sense (i.e., meaning having the potential to), ratherthan the mandatory sense (i.e., meaning must). Additionally, the terms“including,” “having,” “involving,” “containing,” “characterized by,” aswell as variants thereof (e.g., “includes,” “has,” and “involves,”“contains,” etc.), and similar terms as used herein, including theclaims, shall be inclusive and/or open-ended, shall have the samemeaning as the word “comprising” and variants thereof (e.g., “comprise”and “comprises”), and do not exclude additional, un-recited elements ormethod steps, illustratively.

As used in this specification and the appended claims, the singularforms “a,” “an” and “the” each contemplate, include, and specificallydisclose both the singular and plural referents, unless the contextclearly dictates otherwise. For example, reference to an “analyte”contemplates and specifically discloses one, as well as two or moreanalytes.

Various aspects of the present disclosure can be illustrated bydescribing components that are coupled, attached, connected, and/orjoined together. As used herein, the terms “coupled”, “attached”,“connected,” and/or “joined” are used to indicate either a directassociation between two components or, where appropriate, an indirectassociation with one another through intervening or intermediatecomponents. In contrast, when a component is referred to as being“directly coupled”, “directly attached”, “directly connected,” and/or“directly joined” to another component, no intervening elements arepresent or contemplated. Thus, as used herein, the terms “connection,”“connected,” and the like do not necessarily imply direct contactbetween the two or more elements. In addition, components that arecoupled, attached, connected, and/or joined together are not necessarily(reversibly or permanently) secured to one another. For instance,coupling, attaching, connecting, and/or joining can comprise placing,positioning, and/or disposing the components together or otherwiseadjacent in some implementations.

As used herein, directional and/or arbitrary terms, such as “top,”“bottom,” “front,” “back,” “rear,” “left,” “right,” “up,” “down,”“upper,” “lower,” “inner,” “outer,” “internal,” “external,” “interior,”“exterior,” “proximal,” “distal,” and the like can be used solely toindicate relative directions and/or orientations and may not otherwisebe intended to limit the scope of the disclosure, including thespecification, invention, and/or claims.

It will also be appreciated that where two or more values, or a range ofvalues (e.g., less than, greater than, at least, and/or up to a certainvalue, and/or between two recited values) is disclosed or recited, anyspecific value or range of values falling within the disclosed values orrange of values is likewise specifically disclosed and contemplatedherein. Thus, disclosure of an illustrative measurement (e.g., length,width, thickness, etc.) that is less than or equal to about 10 units orbetween 0 and 10 units includes, illustratively, a specific disclosureof: (i) a measurement of 9 units, 5 units, 1 units, or any other valuebetween 0 and 10 units, including 0 units and/or 10 units; and/or (ii) ameasurement between 9 units and 1 units, between 8 units and 2 units,between 6 units and 4 units, and/or any other range of values between 0and 10 units.

1. In the present disclosure, example systems, methods, and/or apparatusmay be described with reference to one or more analytes or analytemolecules (of interest). It should be appreciated that as used herein,“analyte” can refer to a substance whose chemical constituent(s) arebeing analyzed (e.g., detected, isolated, separated, identified,measured, quantified, etc.) and/or the chemical constituent(s)themselves (i.e., a chemical substance that is the subject of chemicalanalysis, a substance or chemical constituent that is of interest in ananalytical procedure, etc.). Thus, an illustrative fluid (e.g., drinkingwater) sample can be and/or constitute an analyte having or comprisingone or more analyte molecules of interest disposed or contained therein.Alternatively or in addition, the one or more analyte molecules ofinterest disposed or contained in the drinking water sample can likewiseconstitute analyte(s). Thus, where appropriate, an analyte (i.e., fluidsample) can be introduced into a chromatography member (e.g.,concentrator and/or analytical column) configured to retain the analyte(i.e., molecule(s) of interest) in one or more embodiments.

2. Moreover, as used herein, a “molecule” or “molecule of interest”includes other matter of interest, including but not limited to cells,particles, compounds, crystals, aggregates, etc. For instance, in atleast one embodiment, a molecule of interest can comprise phosphate,sulfate, nitrate, nitrite, bromate, chlorite, or another molecularcompound, including acids, hydrocarbons, and the like. In otherembodiments, a molecule of interest can comprise a (charged) elementalmolecule, such as fluoride, chloride, bromide, arsenic, barium,chromium, etc., as well as compounds including the same. Thus, referenceto a “molecule” or “molecule of interest” should not be construed asbeing limited to a (single) molecule, per se. Rather, such terms shouldbe construed broadly to include any substance or matter (e.g., that maybe present or included in a liquid sample).

In addition, example systems, methods, and/or apparatus may be describedwith reference to one or more ions, ionic molecules, ionized molecules,charged molecules, and the like. It will be appreciated that such termsare illustrative and/or representative of analytes, in general, andshould be understood accordingly.

As used herein, “ion exchange barrier,” and similar terms may include,without limitation, an ion exchange membrane in the form of thin sheets,a stack of ion exchange membranes, an ion exchange cylinder, or an ionexchange connector as known in the art and/or described herein.

It is further to be understood that some of the drawings includedherewith, and which are referenced herein, are diagrammatic andschematic representations of example embodiments, and are not limitingof the present disclosure. Moreover, while various drawings are providedat a scale that is considered functional for some embodiments, thedrawings are not necessarily drawn to scale for all contemplatedembodiments. It should be understood that the scale may be varied andthe illustrated embodiments are not necessarily drawn to scale for allembodiments encompassed herein. Accordingly, no inference should bedrawn from the drawings as to the necessity of any scale.

Furthermore, in the exemplary embodiments illustrated in the figures,like structures will be provided with similar reference designations,where possible. Specific language will be used herein to describe theexemplary embodiments. Nevertheless it will be understood that nolimitation of the scope of the disclosure is thereby intended. It is tobe understood that the drawings are diagrammatic and schematicrepresentations of various embodiments of this disclosure, and are notto be construed as limiting the scope of the disclosure, unless suchshape, form, scale, function, or other feature is expressly describedherein as essential.

While the detailed description is separated into sections, the sectionheaders and contents within each section are not intended to beself-contained descriptions and embodiments. Rather, the contents ofeach section within the detailed description are intended to be read andunderstood as a collective whole where elements of one section maypertain to and/or inform other sections. Accordingly, embodimentsspecifically disclosed within one section may also relate to and/orserve as additional and/or alternative embodiments in another sectionhaving the same and/or similar systems, devices, methods, and/orterminology.

Analyte Detection System and Methods

Certain embodiments of the present disclosure relate generally tosystems and methods for detecting and quantifying one or more analytemolecules of interest. For example, the following describes a generalchromatography system suitable for use with some embodiments of thechromatography columns and methods described herein. FIG. 1 illustratesan embodiment of an ion chromatography system 500 that includes a pump502, an electrolytic eluent generating device 503, a degas assembly 510,an injection valve 512, a chromatography separation device 514, asuppressor 515, a detector 516, and a microprocessor 518. A recycle line520 may be used to transfer the liquid from an output of detector 516 toa regenerant portion of suppressor 515, and then to an inlet of degasassembly 510.

Pump 502 can be configured to pump a liquid from a liquid source and befluidically connected to electrolytic eluent generating device 503.Electrolytic eluent generating device 503 is configured to generate aneluent such as for example KOH or methanesulfonic acid. Detailsregarding electrolytic eluent generating devices (e.g., eluentgenerator) can be found in U.S. Pat. Nos. 6,225,129 and 6,682,701, whichare hereby incorporated by reference herein. In an embodiment, aresidual gas may be carbon dioxide, hydrogen, and oxygen. The gas can beswept out of degas assembly 510 using a recycled liquid via a recycleline 520 that is downstream of detector 516. Injection valve 512 can beused to inject an aliquot of a liquid sample into an eluent stream.Chromatography separation device 514 (e.g., chromatography column) canbe used to separate various matrix components present in the liquidsample from the analytes of interest. An output of chromatographyseparation device 514 can be fluidically connected to suppressor 515,and then to detector 516 to measure the presence of the separatedchemical constituents of the liquid sample.

Suppressor 515 is a device used in ion chromatography to remove theeluent and sample counter ions and replace them with regenerant ions. Asa result, the eluent is converted to a weakly dissociated form prior toentering the detector. The suppressor allows analyte ions to be detectedwith a conductivity detector with a low background. Furthermore, theanalytes can be converted to the more conductive acid or base form,which enhances the signal, particularly for fully dissociated species.Detail regarding suppressors can be found in U.S. Pat. Nos. 4,999,098;6,328,885; and 8,415,168 which are hereby fully incorporated byreference herein.

Detector 516 may be in the form of ultraviolet-visible spectrometer, afluorescence spectrometer, an electrochemical detector, a conductometricdetector, a charge detector, or a combination thereof. Details regardingthe charge detector that is based on a charged barrier and twoelectrodes can be found in US Pre-Grant Publication No. 20090218238,which is hereby fully incorporated by reference herein. For thesituation where recycle line 520 is not needed, detector 516 may also bein the form of a mass spectrometer or a charged aerosol detector. Thecharged aerosol detector nebulizes the effluent flow and creates chargedparticles that can be measured as a current proportional to the analyteconcentration. Details regarding the charged aerosol detector can befound in U.S. Pat. Nos. 6,544,484; and 6,568,245, which are hereby fullyincorporated by reference herein.

An electronic circuit may include microprocessor 518 and a memoryportion. Microprocessor 518 can be used to control the operation ofchromatography system 500. Microprocessor 518 may either be integratedinto chromatography system 500 or be part of a personal computer thatcommunicates with chromatography system 500. Microprocessor 518 may beconfigured to communicate with and control one or more components ofchromatography system such as pump 502, electrolytic eluent generatingdevice 503, injection valve 512, and detector 516. Note thatchromatography system 500 is a particular machine used to analyzestandard solutions and sample solutions to identify chemicalconstituents and the associated concentration values.

Eluent Generator Systems and Methods

FIGS. 2A and 2B illustrate two exemplary eluent generation systems orcomponents according to certain embodiments of the present disclosure.Further details and examples of such systems or components are disclosedin references previously cited and incorporated by reference herein.

FIG. 2A depicts an eluent generation system for cation hydroxide thatincludes a pump 120, an eluent generator cartridge 130, a trap column140, and a degas module 105. The eluent generator cartridge 130 has alow pressure electrolyte reservoir 130 d (or ion source reservoir), ahigh pressure eluent generation chamber 130 e, and an ion exchangeconnector or membrane 130 f (e.g., disposed between the electrolytereservoir 130 d and the eluent generation chamber 130 e). As depicted,electrolyte reservoir 130 d contains a fluid ion source with eluentcounter ions (or species ions)—e.g., K⁺, Na⁺, or Li⁺, and also containscorresponding hydroxide ions, in the present embodiment. The counterions and corresponding hydroxide ions can be at any suitable startingconcentration (e.g., typically about 2-4 N).

In some embodiments, the eluent generation chamber 130 e can bepressurized. For instance, the eluent generation chamber 130 e can bepressurized and maintained at a pressure of about 100 to about 15000psi, preferably about 1000 to about 5000 psi. As depicted in FIG. 2A,ion source reservoir 130 d has a vent 131 that is open to ambientpressure.

The ion exchange barrier, connector or membrane 130 f can comprise aspecies ion-permeable membrane. For instance, the ion exchange connectoror membrane 130 f can comprise a cation exchange membrane that permitsthe transport of the cations. The ion exchange connector or membrane 130f can substantially prevent liquid flow and, preferably, reducing anionpassage through the cation exchange membrane while providing an iontransport bridge that permits the transport of the cationic eluentcounter ions from the (low-pressure) ion source reservoir 130 d to the(high-pressure) eluent generation chamber 130 e. Accordingly, the eluentgeneration chamber 130 e is isolated or fluidly separated from the ionsource reservoir 130 d by the ion exchange membrane 130 f. Ion exchangemembrane 130 f can be in form of a stack of multiple membranes. Thesystem also includes a source electrode 130 a (e.g., perforated platinumfoil or platinum wire) in electrical communication with or disposed inthe ion source disposed in the ion source reservoir 130 d and agenerator electrode 130 b (e.g., perforated platinum foil or platinumwire) in electrical communication with or disposed in the eluentgeneration chamber 130 e and/or an liquid (e.g., concentrator effluentor water, such as deionized water) disposed therein.

During (normal) operation of a KOH eluent generation component, asfurther depicted in FIG. 3A, for example, the liquid (eluent) stream(e.g., deionized water) flows through the (high-pressure) KOH eluentgeneration chamber so as to be in communication with the generatorelectrode, which serves or functions as a cathode in the presentembodiment. In response to a voltage having a first polarity appliedacross the electrodes (or current or charge flow in a first directionbetween the electrodes), the generator electrode produces eluent ions(OH⁻, in the present embodiment) and hydrogen gas in the eluentgeneration chamber through a water-splitting reaction (i.e., waterreduction reaction). Similarly, the reservoir electrode, which serves orfunctions as an anode in the present embodiment, produces H⁺ or H₃O⁺, inthe present embodiment, and oxygen gas in the ion source reservoirthrough water-splitting reaction (i.e., water oxidation reaction) inresponse to the first polarity voltage (or first direction current orcharge flow).

Referring back to FIG. 3A, application of an electric field between the(low-pressure) electrolyte reservoir and the KOH generation chamberdrives (or promotes) transport of eluent counter ions (K⁺, in thepresent embodiment) from the source reservoir, across the ion exchangeconnector (comprising a cation exchange membrane in the presentembodiment), and into the generation chamber. Specifically, H⁺ or H₃O⁺ions generated at the anode combines with the hydroxide to form waterwhile K⁺ ions migrate in the electrolyte reservoir and move towards thecathode. For each hydronium ion being formed in the electrolytereservoir, one K⁺ can be displaced and migrate across the cationexchange membrane into the eluent generation chamber, where the eluentcounter ions combine with the produced ⁻OH eluent ions generated at thecathode to form KOH eluent solution, which can be used as the eluent foranion exchange chromatography. The hydronium formed in the electrolytereservoir reacts with a hydroxide ion in the electrolyte reservoir toform water. The hydroxide generated in the eluent generation chambermostly remains in that chamber as the cation exchange membrane inhibits(e.g., reduces or substantially reduces) the transport of negativelycharged ions. The extent to which the cation exchange membrane inhibitsanion transport is dependent upon the concentration of the electrolytein the reservoir and the concentration of the ion exchange sites in themembrane. The closer these two concentrations are, the greater the aniontransport rate. The concentration of generated KOH is proportional tothe magnitude of the current flowing to the generator component oracross the electrodes and the eluent stream (e.g., water) flow ratethrough the generation chamber. Therefore, given the eluent stream flowrate, the eluent generator module can accurately and reproduciblygenerate KOH at one or more desired concentrations based on an inputcurrent. The continuously flowing water stream carries the generatedeluent out of the cartridge.

The eluent-containing stream can then flow through one or more furtherprocessing components (e.g., trap column 140, degasser 105, etc.) andinto an anion exchange chromatography column to elute retained analytemolecules of interest, as known in the art. In some embodiments, thechromatography column can be a concentrator column for retaininganalytes of interest to be eluted in a smaller volume than that of theintroduced analyte stream, as known in the art. In some embodiments, thechromatography column can be an analytical column for separate elutionof retained analytes of interest for analytical detection (e.g.,conductivity or other measurement), as known in the art. It will beappreciated that the above description for the generation of KOH eluentcan be applied to the generation of NaOH, LiOH, or other suitableeluent.

FIG. 3B is a schematic representing an eluent generator in a passivemode or turned off where neither the liquid is flowing through thegeneration chamber nor the voltage (or current) is applied to theelectrodes. In this situation, passive diffusion can occur because ofthe relatively large concentration differential between the KOH in theelectrolyte reservoir (2-4 N) and the non-flowing deionized water in theKOH generation chamber. Since the volume of the KOH generation chamberis relatively small, the liquid is quiescent, and the passive mode canbe for an extended period of time (e.g. several hours), the build of uppassively diffused KOH can be significant and interfere with the ionchromatographic analysis. It should be noted that a flowing liquidreduces the effects of passive diffusion of KOH because it does not havea chance to build up in the generation chamber. The above descriptionfor the generation of hydroxide eluent can be applied to the generationof acid. FIG. 2B depicts an alternative embodiment in which reservoir130 d contains the eluent counter ion methanesulfonate species ions(MSA⁻) and ion exchange connector or membrane 130 f comprises an anionexchange connector having an anion exchange membrane that permits thepassage of anions while reducing the passage of cations and fluid. Inthis embodiment, the reservoir electrode 130 a serves or functions as acathode and the generation chamber electrode 130 b serves or functionsas an anode during normal operation. The water splitting reaction (i.e.,water reduction reaction) generates OH⁻ ions in the reservoir, whichcombine with H⁺ already in the reservoir to form water, while thepotential drives MSA⁻ species ions in the electrolyte reservoir into theeluent generation chamber. Thus, the electric field between the twoelectrodes causes the MSA⁻ species ions to migrate through or across theanion exchange membrane and into the eluent generation chamber. Themigrated MSA⁻ ions combine with electrolytically produced H⁺ eluent ionsgenerated at the anode in the eluent generation chamber through the(anodal) water splitting reaction (i.e., water oxidizing reaction), toproduce a methanesulfonic acid (MSA) solution, which can be used as theeluent for cation exchange chromatography.

The concentration of generated MSA is proportional to the magnitude ofthe current flowing to the generator component or across the electrodesand the eluent stream (e.g., water) flow rate through the generationchamber. Therefore, given the eluent stream flow rate, the eluentgenerator module can accurately and reproducibly generate MSA at one ormore desired concentrations. The continuously flowing water streamcarries the generated eluent out of the cartridge.

The eluent-containing stream can then flow through one or more furtherprocessing components (e.g., trap column 140, degasser 105, etc.) andinto a cation exchange chromatography column to elute retained analytemolecules of interest therefrom, as known in the art. In someembodiments, the chromatography column can be a concentrator column forretaining analytes of interest to be eluted in a smaller volume thanthat of the introduced analyte stream, as known in the art. In someembodiments, the chromatography column can be an analytical column forseparate elution of retained analytes of interest for analyticaldetection (e.g., conductivity or other measurement), as known in theart. It will be appreciated that the above description of a generatorused for the generation of MSA eluent can be applied to the generationof other suitable eluents.

Thus, in normal operation (see FIG. 3A), a first polarity voltageapplied across the electrodes electrolytically generates hydroxide orhydronium ions at the first side of the ion exchange membrane (e.g., inthe reservoir). The negatively charged hydroxide is generated in thereservoir when the eluent counter ion (e.g., MSA⁻) is negativelycharged. Similarly, the positively charged hydronium is generated in thereservoir when the eluent counter ion (e.g., K⁺) is positively charged.The first polarity voltage also generates an electric field thatpromotes the translocation of species ions (eluent counter ions) acrossthe ion exchange membrane from the first (reservoir) side 802 to thesecond (chamber) side 804. Accordingly, at least one embodiment caninclude applying a voltage across a first electrode 130 a and a secondelectrode 130 b, the voltage having a first polarity, the first andsecond electrodes being disposed, respectively, on first and secondsides of an ion exchange membrane, the applied voltage with the firstpolarity electrolytically generating hydronium ions at the first side ofthe ion exchange membrane, the electric field promoting thetranslocation of eluent counter ions through the ion exchange membranefrom the first side to the second side.

Embodiments of the present disclosure can also include selectivelyreversing the polarity of the voltage applied between the electrodesfrom the first polarity to a second polarity. Accordingly, the secondpolarity can be opposite the first polarity, as understood by thoseskilled in the art. The electric field generated by applying the secondpolarity voltage (i) drives eluent counter ions from the second(chamber) side to the first (reservoir) side (i.e., across the ionexchange membrane) and/or (ii) inhibits translocation of the eluentcounter ions and/or eluent through the ion exchange membrane from thefirst side to the second side, preferably thereby inhibitingaccumulation of the eluent counter ions and/or eluent on the secondside. Applicant has observed a decrease in the passive diffusion ofeluent across the ion exchange barrier from the electrolyte reservoir tothe generation chamber during the application of the reverse biaselectric field. As such, without being bound by any theory, the reversebias electric field inhibits the passive diffusion of eluent across theion exchange barrier.

For instance, when the polarity of the voltage is selectively reversedfrom the first polarity to the second polarity, the eluent generationchamber may contain an amount of the same electrolyte(s) that arepresent in the source ion reservoir. By way of example, the eluentgeneration chamber may contain hydroxide electrolytically generated inthe eluent generation chamber and/or eluent counter cation (e.g., K⁺,Na⁺, or Li⁺) transported from the reservoir to the chamber by means ofthe electric field generated by the first polarity voltage appliedduring normal operation mode, as described above. In the above cationhydroxide example, selectively reversing the polarity of the voltagefrom the first polarity to the second polarity can inhibit thetranslocation of eluent from the electrolyte reservoir through the ionexchange barrier and to the generation chamber. In addition, undercertain circumstances, the second polarity may also electrolyticallygenerate hydronium ions at the second (chamber) side of the ion exchangemembrane and/or in the eluent generation chamber (or fluid disposedtherein). In this reversed polarity mode, the hydronium ions can reactwith hydroxide present in the eluent generation chamber to form water,thereby driving the eluent counter cation towards the reservoirelectrode—now cathode—to maintain charge balance.

Illustratively, the KOH eluent generation component depicted in FIG. 3Acan be switched or disposed in a reverse bias mode, as depicted in FIG.3C, in which the anode (reservoir electrode) depicted in FIG. 3A servesor functions as a cathode and the cathode (chamber electrode) depictedin FIG. 3A serves or function as an anode. In this reverse biasconfiguration, the water splitting reaction at the chamber electrode—nowanode—generates H⁺ or H₃O⁺ in the present embodiment. Passive diffusionof KOH from the electrolyte reservoir to the KOH generation chamber canoccur because of the relatively large concentration differential betweenthe KOH in the electrolyte reservoir (2-4 N) and the non-flowingdeionized water in the KOH generation chamber. The generated hydroniumions can neutralize at least some, and preferably all of the OH⁻ ions ofthe passively diffused KOH molecules to form H₂O and then transfer theremaining K⁺ ion to the membrane towards the cathode (to maintain chargebalance). In a preferred embodiment, a suitable voltage can be selectedto match the rate of ion diffusion with the rate of ion transport,thereby optimizing the form of the membrane. Accordingly, in certainembodiments, an equilibrium can be achieved between passive iondiffusion into the chamber and active reverse bias potential into thereservoir, such that little to no hydronium enters the membrane and nopotassium exits the membrane (e.g., on either side).

In some embodiments, where the fluid in the eluent generation chamber isessentially deionized water that does not contain passively diffusedKOH, the electrolytically generated hydronium can migrate to themembrane towards the cathode converting the membrane to the hydroniumform and in the process ejecting K⁺ into the electrolyte reservoir.Without being bound to any theory, each hydronium ion that enters themembrane stack causes a (K⁺) species ion or electrolytically-generatedion (e.g., H⁺ or H₃O⁺) to exit the membrane stack into the reservoir(e.g., to achieve a charge and/or concentration balance).

It should also be noted that by transforming the ion exchange membraneinto the hydronium form, ion exchange retention of potassium is possiblewhen passive diffusion of KOH occurs on the membrane resulting information of water. The net effect of the reversed polarity is minimaltransport of the KOH.

Thus, without being bound to any theory, the generation of an electricfield can inhibit translocation of eluent and/or eluent counter ionsthrough the membrane and/or into the chamber. In particular, generationof hydronium ions in the chamber can neutralize partly or all of the OH⁻ions of the KOH that passively diffused from the electrolyte reservoirto the non-flowing generation chamber.

In some embodiments, the first electrode is in electrical communicationwith a liquid ion source disposed in an ion source reservoir at thefirst side of the ion exchange membrane, the eluent counter ions beingdisposed in the liquid ion source. The second electrode can likewise bein electrical communication with a liquid disposed in an eluentgeneration chamber at the second side of the ion exchange membrane. Theapplied voltage with the first polarity electrolytically generates afirst electric field that promotes translocation of the eluent counterions through the ion exchange membrane toward the second electrode.Similarly, the applied voltage with the second polarity electrolyticallygenerates the second electric field that inhibits the eluent counterions in the ion source reservoir from translocating through the ionexchange membrane.

As described above, the (normal operation) voltage having the firstpolarity can cause the first electrode to function as an anode and thesecond electrode to function as a cathode, while the (reverse bias)voltage having the second polarity causes the first electrode tofunction as a cathode and the second electrode to function as an anode.The foregoing configuration is applicable for eluent generationcomponents corresponding or similar to those depicted in FIG. 2A andFIG. 3A where the eluent ion is negative (e.g. hydroxide) and thecounter ion is positively charged (e.g., K⁺), they combine to form theeluent (e.g., KOH). In such embodiments, the electrolytically generatedions in the electrolyte reservoir can be or comprise positively-chargedions. For instance, the positively-charged ions can be or comprise H⁺ orhydronium ions.

Alternatively, the (normal operation) voltage having the first polaritycan cause the first electrode to function as a cathode and the secondelectrode to function as an anode, while the (reverse bias) voltagehaving the second polarity causes the first electrode to function as ananode and the second electrode to function as a cathode. The foregoingconfiguration is applicable for eluent generation componentscorresponding or similar to those depicted in FIG. 2B where the eluention is positively charged (e.g. H⁺) and the counter ion is negativelycharged (e.g., methanesulfonate; MSA⁻) that combine to form the eluent(e.g., methanesulfonic acid). In such embodiments, the electrolyticallygenerated ions can be or comprise negatively-charged ions. For instance,the negatively-charged ions can be or comprise hydroxide ions.

As described above, the production of an electric field can prevent,reduce, inhibit, control, and/or regulate the translocation of eluentand/or species ions through the ion exchange membrane. By way of furtherexplanation, the (reverse bias) voltage having the second polarity canbe adjusted—increased or decreased. Just as increasing the (normaloperation) voltage having the first polarity can increase the magnitudeof the first electric field as known in the art, increasing an absolutemagnitude of the (reverse bias) voltage can also increase the magnitudeof the electric field, the amount of electrolytic ions capable ofneutralizing passively diffused eluent molecules from the electrolytereservoir to the generation chamber, and the amount of electrolytic ionscapable of entering the ion exchange membrane from the generationchamber. In addition, increasing an absolute magnitude of the (reversebias) voltage may improve the inhibition and reduce the amount of eluentthat passively diffuses from the electrolyte reservoir to the generationchamber. Accordingly, certain embodiments can includeadjusting—increasing and/or decreasing—the (normal operation) voltagehaving the first polarity and/or the (reverse bias) voltage having thesecond polarity (e.g., in order to control, regulate, increase, ordecrease the electric field). Accordingly, certain embodiments caninclude adjusting the voltage having the second polarity so that aportion of the of the diffused eluent molecules that diffused from theelectrolyte reservoir to the generation chamber are neutralized withelectrolytically generated ion in the generation chamber where theportion may be 100%, at least 99%, at least 95%, at least 90%, at least80%, at least 70%, at least 60%, at least 50% of the diffused eluentmolecules.

Some embodiments can include a step of selectively reversing thepolarity of the voltage from the second polarity to the first polarity.The (reverse bias) voltage having the second polarity can be appliedduring equipment down time, passive mode(s), transportation, delaymode(s), and so forth. The second polarity can be a standby voltage thatcould be invoked when the eluent generator cartridge is not being usedto generate eluent. However, resuming back to the first normal polarity,the device can generate eluent. Such events can occur for brief orextended periods of time. Accordingly, some embodiments can includewaiting a first period of time before selectively reversing the polarityof the voltage from the second polarity to the first polarity and/orwaiting a first period of time between the step of selectively reversingthe polarity of the voltage from the first polarity to a second polarityand the step of selectively reversing the polarity of the voltage fromthe second polarity to the first polarity. Some embodiments can furtherinclude another step of selectively reversing the polarity of thevoltage from the first polarity to the second polarity.

In some cases, a large amount of electrolytic ions can be generated inthe generation chamber during the reverse bias mode that converts themembrane to either the hydronium (for the case of KOH generator) orhydroxide form (for the case of MSA generator). Although this state isadvantageous for the membrane in inhibiting translocation of eluentcounter ions, upon startup or resuming normal polarity, the device cantake a long time to stabilize the startup operation since the membraneneeds to be regenerated from the hydronium or hydroxide state to beingcharged with eluent counter ions. This delay in system startup time canbe reduced or avoided by optimizing the magnitude of the applied voltageand/or the duration of the applied voltage for a particular the membranein an empirical manner, which can depend on whether the particularmembrane has a relatively high or low ion exchange capacity. Anotheroption is to selectively reverse the polarity when the eluent counterions are detected close to the membrane electrode interface. One meansof detection can be by electrical means by measuring the resistanceacross another pair of sensor electrodes in the generation chamber. Theresistance would be high when no translocation species is detected butwill become low when the eluent counter ions are detected. The polaritycan be reversed once the species is detected to inhibit the transport ofthe species ions. Thus a reverse bias or polarity can be invoked whenthe device needs it for efficient operation. This type of approach wouldbe useful when transporting the eluent generator cartridge and thedevice can be shipped with this automated reverse bias feature tofacilitate fast startup upon installation or standby.

In at least one embodiment, a method of inhibiting translocation ofeluent counter ions through an ion exchange membrane can compriseapplying a voltage across a first electrode and a second electrode, thefirst electrode being disposed on a first side of an ion exchangemembrane, the second electrode being disposed on a second side of theion exchange membrane, the applied voltage generating an electric fieldthat inhibits translocation of species ions through the ion exchangemembrane from the first side to the second side. The voltage can have apolarity. The first electrode can be in electrical communication with aliquid ion source. The liquid ion source can be disposed in an ionsource reservoir at the first side of the ion exchange membrane. Theeluent counter ions can be disposed in the liquid ion source.

The second electrode can be in electrical communication with a liquid.The liquid can be disposed in an eluent generation chamber at the secondside of the ion exchange membrane. The applied voltage (with thepolarity) can generate an electric field that inhibits the eluentcounter ions in the ion source reservoir from translocating through theion exchange membrane. Accordingly, some embodiments can includeproviding or obtaining a source of species ions. Some embodiment caninclude providing or obtaining a first electrode and a second electrode.Some embodiment can include providing or obtaining an ion exchangemembrane. The first and second electrodes can be disposed on oppositesides of the ion exchange membrane. Embodiments can further includeselectively reversing the polarity of the voltage. The reversed polarityvoltage can comprise a normal operational polarity voltage as known inthe art. For instance, the reversed, normal operational polarity voltageapplied across the first and second electrodes can electrolyticallygenerate hydronium or hydroxide at the first side of the ion exchangemembrane.

Some embodiments can include waiting a first period of time beforeselectively reversing the polarity of the voltage. The first period oftime can be greater than or equal to about 1-60 minutes, 1-24 hours,1-30 days, or any period of time or range of time disposed therebetween.For instance, the first period of time can be up to, greater than orequal to, or between about 1 hour, 2 hours, 4 hours, 8 hours, 12 hours,16 hours, 24 hours, 36 hours, 48 hours, 60 hours, 72 hours, 84 hours, 90hours, 96 hours, 108 hours, 120 hours, and so forth. In someembodiments, the waiting period of time can be the time required for thetranslocation of the species to a given sensor location. In someembodiments, the waiting period of time can be the time between the endof a work shift of the analyst and the beginning of a subsequent workshift (e.g. overnight, over a weekend, etc.). In some embodiments, thewaiting period of time can be a period of time in which samples are notbeing analyzed.

In the normal operational mode, where eluent counter ions aretransported through the ion exchange membrane under influence of anelectric field, the eluent generation system or component can have aliquid flowing through the eluent generation chamber. Generated eluent(e.g., KOH, etc.) can be carried out of the eluent generation chamber bymeans of the aqueous fluid stream. The liquid stream containing eluent(i.e., the eluent stream) can flow to and/or through additional systemcomponents as known in the art.

In the reverse bias mode, where an electric field is generated toinhibit the flow of eluent counter ions into the generation chamber, theliquid flow can be stopped.

One or more embodiments can include initiating a flow of the aqueousfluid through the eluent generation chamber. The initiated flow can beany flow rate suitable for the eluent generation chamber (or cartridge).Illustratively, the flow rate can be between about 0.05 μl/min and about10 ml/min, preferably between about 0.5 μl/min and about 5 ml/min, morepreferably between about 0.5 ml/min and about 2 ml/min.

Certain embodiments can include selectively reversing the polarity ofthe voltage from the first (reverse bias) polarity to a second (normal)polarity. The voltage with the second polarity can generate an electricfield (e.g., a second electric field) that promotes translocation of thespecies ions through the membrane from the first side to the secondside.

One or more embodiments can include initiating a startup procedure,illustratively an automatic startup procedure. The (automatic) startupprocedure can occur over a second period of time. Illustratively, thesecond period of time can be from less than 1 minute to greater than orequal to about 30 minutes in various embodiments. One or moreembodiments can include initiating an equilibration procedure,illustratively an automatic equilibration procedure. The (automatic)equilibration can occur over a third period of time. Illustratively, thethird period of time can be less than or equal to about 60 minutes,preferably less than or equal to about 45 minutes, more preferably lessthan or equal to about 30 minutes, still more preferably less than orequal to about 15 minutes, still more preferably less than or equal toabout 10 minutes. Accordingly, one or more embodiments can includeequilibrating the eluent generation module over a (third) period oftime. The (third) period of time can be less than or equal to about 60minutes, preferably less than or equal to about 45 minutes, morepreferably less than or equal to about 30 minutes, still more preferablyless than or equal to about 15 minutes, still more preferably less thanor equal to about 10 minutes.

In some embodiments, the reverse bias of the present disclosure canprovide a significant reduction in system startup and/or equilibrationtime. For instance, at least one standard analyte detection systemand/or eluent generation module thereof can require a substantial amountof time and aqueous fluid to equilibrate the system and/or componentsthereof (e.g., prior to injection of analyte ions to be identifiedand/or quantified). Standard equipment startup times can be between 1minute and 10 minutes, typically about 5 minutes. Where pre-startup downtime was for an extended period, such as between 16 hours and 90 hours,or more, a high concentration ion plug disposed in the eluent generationchamber may transit system components during startup. Additionalequilibration time can be required in order to achieve a suitablebaseline measurement for one or more parameters, such as conductivity,in the aqueous fluid (eluent) stream, prior to injection of analyte ionsinto the system. In some embodiments, the suitable baseline measurementcomprises a conductivity less than or equal to 0.25, 0.2, 0.19, 0.18,0.175, 0.17, 0.165, 0.16, 0.155, 0.15, 0.145, 0.14, 0.135, or less(μS/cm).

Achieving the suitable baseline measurement after transit of a highconcentration ion plug may require flushing or sweeping the systemcomponents with aqueous fluid at a suitable flow rate for a suitableperiod of time or volume. For instance, suitable flow rates can dependon the size and/or volume of one or more system components—e.g., columnsize, loop size, line/tubing size, etc. Illustratively, suitable flowrates of typical systems can be between about 0.005 ml/min and about 5ml/min, preferably between about 0.01 ml/min and about 1 ml/min. Forinstance, in some embodiments, suitable flow rates for a 2 mm internaldiameter column can be, preferably, between about 0.15 ml/min and about0.5 ml/min, still more preferably between about 0.2 ml/min and about 0.4ml/min, still more preferably between about 0.25 ml/min and about 0.35ml/min, still more preferably about 0.3 ml/min. In some embodiments,suitable flow rates for a 4 mm internal diameter column can be,preferably, about 1 ml/min, more preferably about 1.5 ml/min. In someembodiments, suitable flow rates for a capillary column can be,preferably, about 0.01 ml/min. Accordingly, suitable flow rates may varydepending on the size and/or configuration of the system and/orcomponent(s). Under suitable conditions, the equilibration time requiredto reach a suitable baseline after transit of a high concentration ionplug can be greater than or equal to about 10 minutes, 15 minutes, 20minutes, 30 minutes, 45 minutes, 60 minutes, 90 minutes, 120 minutes,150 minutes, 180 minutes, 210 minutes, 240 minutes, 270 minutes, 285minutes, 300 minutes, 315 minutes, 330 minutes, 360 minutes, 390minutes, 405 minutes, or more.

Unlike standard down time, passive modes—where the electrical componentsand/or fluid flow are inactive, embodiments of the present disclosurecan include a reverse voltage bias mode in which the normal polarity ofthe voltage during system operation is reversed during down time. In atleast some embodiments, during reverse voltage bias mode operation, theflow of liquid through the eluent generation chamber can be stopped.Following a similar extended period (e.g., between about 16 hours to 90hours, or more), under similar startup and operation parameters,embodiments of the present disclosure can decrease system equilibrationtimes by at least 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%, 55%, 60%,70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98%, 98.5%, or 99%. Forinstance, embodiments of the present disclosure can require less than orequal to about 400 minutes, 300 minutes, 200 minutes, 100 minutes, 90minutes, 60 minutes, 55 minutes, 50 minutes, 45 minutes, 40 minutes, 35minutes, 30 minutes, 25 minutes, 20 minutes, 15 minutes, 12 minutes, 10minutes, 9 minutes, 8 minutes, 7 minutes, 6 minutes, 5 minutes, 4minutes, 3 minutes, 2 minutes, or 1 minute, or less, of additionalsystem equilibration time (over the normal system startup time). Atleast one embodiment can enable a reduced system startup time of betweenabout 1 minute and about 60 minutes, preferably between about 2 minutesand about 20 minutes, more preferably between about 3 minutes and about45 minutes, still more preferably between about 4 minutes and about 30minutes, still more preferably between about 5 minutes and about 20minutes. Such time savings result in significant operational and laborcost savings, such as reagent (aqueous fluid or water) costs,electricity costs, personnel costs, and so forth.

Some embodiments can include a system for inhibiting translocation ofspecies ions through an ion exchange membrane. The system can include afirst electrode and a second electrode. The first electrode can be inelectrical communication with an ion source, such as a liquid ionsource. The ion source can be disposed in an ion source reservoir. Theion source can contain species ions (or eluent counter ions). The secondelectrode can be in electrical communication with a liquid. The liquiddisposed in and/or flowing through an eluent generation chamber.

Embodiments can include an ion exchange membrane. The first electrodecan be disposed on a first side of the membrane. The second electrodecan be disposed on a second (e.g., opposite) side of the membrane. Forinstance, the membrane can be disposed between the ion source reservoirand the eluent generation chamber in some embodiments. The membrane canbe selectively permeable to a type of ion—anions or cations, forexample. As understood by those skilled in the art, the membrane cansubstantially prevent liquid flow (therethrough) while providing an iontransport bridge. For instance, the membrane can be structurallyconfigured to substantially prevent liquid flow therethrough. As usedherein, “substantially preventing liquid flow” means that the membranepermits, or is configured to permit, liquid flow therethrough at a rateof less than or equal to 1%, preferably less than or equal to 0.1% ofthe intended operating range of flow rate value(s), or range thereof(e.g., between 0.5 μl/min and 5 ml/min). Those skilled in the art canselect the particular membrane specification suitable for their intendeduse.

As described above, when a (normal operation) voltage having a firstpolarity is applied across the first and second electrodes, a firstelectric field is generated and the eluent counter ions (in the ionsource) are driven through the ion exchange membrane (into the liquid).Similarly, when a reverse bias voltage having a second polarity isapplied across the first and second electrodes, a second electric fieldis generated and eluent counter ions are inhibited from being driventhrough the ion exchange membrane (into the liquid).

Embodiments can also include means for reversing the polarity of thevoltage across the first and second electrodes. Means for reversing thepolarity of the voltage across the first and second electrodes caninclude a switch, such as a polarity-reversing switch. The switch cancomprise a single pole, double throw (SPDT) switch, a double pole,double throw (DPDT) switch, a DPDT rocker switch, or other switch, asknown in the art. In some embodiments, the means for reversing thepolarity of the voltage can be disposed as a part of the eluentgenerator. The switch, for example, can be part of the eluent generator.In other embodiments, the switch can be disposed at another suitablelocation or component, such as a circuit board, power source, etc.

Some embodiments can include a system in an active mode or in an idlemode. Some embodiments can include a voltage applied across the firstand second electrodes. As described above, the voltage can have apolarity. The polarity of the voltage can be a first (normaloperational) polarity voltage or a second (reverse bias and/or passivemode) polarity voltage. The voltage having the first polarity can beactively generating hydroxide or hydronium ions (e.g., at the firstelectrode) in the active, normal operational mode. The voltage havingthe second polarity can be actively generating one of the watersplitting ions, which are hydroxide and hydronium ions, (e.g., at thesecond electrode) in the reverse bias mode. The voltage range for thereversed bias polarity (in terms of absolute values) can be <3V, morepreferably <2 V and most preferably <1.5 V. The voltage can be appliedby a DC power supply or an alternating current power supply. The voltagecan be switched or pulsed as needed to facilitate the inhibition of thetranslocation of the species ions as described in the present invention.It is also possible to operate the device in the constant current orpower mode. The current range for the reversed bias polarity (in termsof absolute values) can be <2 milliamperes, more preferably <700microampres, and most preferably <200 microampres. The normal andreversed bias mode of operation could be operated with independent powersupplies. Under certain circumstances where a significant amount ofeluent has not passively diffused through the ion exchange barrier, theapplied voltage can be replaced with an applied current and still besuitable for decreasing the background signal.

At least one embodiment includes a method of shipping or transporting aneluent generator. The method can comprise transporting the eluentgenerator from a first site to a second site. As used herein, a “site”may include a facility, building, room, or any location. Illustratively,the first site or second site can be or comprise a manufacturing site, astorage site, a wholesale or retail site, a receiving site, a user oroperator site, etc. In at least one embodiment, the eluent generator canbe transported from the first site to the second site while a voltagehaving a polarity is applied across the eluent generator. For instance,a battery can be electrically coupled to the eluent generator such thatthe battery applies (or is configured to apply) a voltage having apolarity, the voltage having the polarity inhibiting translocation ofeluent through a barrier of the eluent generator. In some embodiments,the eluent generator can comprise: a first electrode in electricalcommunication with a liquid ion source disposed in an ion sourcereservoir, the liquid ion source containing species ions; a secondelectrode in electrical communication with a liquid disposed in aneluent generation chamber; and an ion exchange barrier disposed betweenthe ion source reservoir and the eluent generation chamber. A batterycan be electrically coupled to the first electrode and to the secondelectrode such that the battery applies (or is configured to apply) thevoltage having the polarity. With the voltage having the polarityapplied across the first and second electrodes, the eluent in the ionsource is/are inhibited from translocating through the ion exchangebarrier into the liquid.

Illustratively, an embodiment can include a method of shipping an eluentgenerator, the eluent generator comprising: a first electrode inelectrical communication with a liquid ion source disposed in an ionsource reservoir, the liquid ion source containing species ions; asecond electrode in electrical communication with a liquid (e.g., wateror deionized water) disposed in an eluent generation chamber; and an ionexchange barrier disposed between the ion source reservoir and theeluent generation chamber such that when a voltage having a firstpolarity is applied across the first and second electrodes the eluentcounter ions in the ion source are driven through the ion exchangebarrier into the liquid, and when a voltage having a second polarity isapplied across the first and second electrodes the eluent in the ionsource are inhibited from translocating through the ion exchange barrierinto the liquid, a battery being electrically coupled to the firstelectrode and the second electrode, in which the battery is configuredto apply the voltage having the second polarity, the method comprisingtransporting the eluent generator from a manufacturing site to areceiving site.

Any prior art eluent generator system can benefit from the presentinvention. While the examples here discuss one format of eluentgeneration, multiple channel devices of the prior art that pursuefunctions that include eluent generation with source reagents wouldbenefit from the polarity reversal.

Those skilled in the art will appreciate that voltage is merely onemeasurement for electrical systems, circuits, etc. It is noted thatalternative measurements, such as electric or electrical potential,current, electromotive force, and so forth, are also contemplatedherein. Accordingly, embodiments of the present disclosure canalternatively include reversing an electric or electrical potential,current, electromotive force, and so forth.

EXAMPLES

The examples disclosed herein are intended to provide support forvarious embodiments of the present disclosure. Subject matter disclosedin one example may relate to any suitable embodiment of the presentdisclosure and is not necessarily limited to the specific example inwhich it is presented.

Example 1

Existing eluent generation systems require a large amount of time tore-start the system after a period of system down time (e.g., powereddown, etc.) in order to reach a suitable baseline. Specifically, eluentcounter or species ions passively diffuse through the membrane of theeluent generation component. Over time, the concentration of ions in theeluent generation chamber becomes substantially higher than theconcentration of eluent ions in the aqueous fluid, eluent stream duringnormal operation. The large concentration of ions in the fluid streammay need to be swept or flushed from the system plumbing components(e.g., lines, valves, etc.) before the system can be operated at optimallevels. Sweeping or flushing the plumbing components of the system canbe time-consuming and require additional monitoring by operationpersonnel or users. The issue is worse when the system equilibrationflow rate is low.

Alternatively, or in addition, the analytical or concentrator column mayrequire additional equilibration time to reach a steady, low, baselinereading (e.g., if the high ion concentration plug transits through thecolumn during or after system start up procedures). The equilibrationtime may be required to achieve optimal system performance. Forinstance, the baseline reading may need to be reached before analyteions can be injected onto the column to ensure optimal or suitablelevels of analyte ion recovery, identification, quantification, etc.Column equilibration may also be affected in other ways. Alternatively,or in addition, the capacity of the ion suppressor (in line downstreamof the eluent generator) can be exhausted by the high ion concentrationplug, requiring additional time for regeneration of the suppressor.Overall, the impact of the high concentration plug includes added systemequilibration time needed for optimal chromatographic operation. Thisadditional time translates into additional labor and operation costs.

FIG. 4 illustrates an example of an eluent generator performance after a16 hour period of system down time (i.e., no voltage applied, no fluidflow, etc.). Depicted is a chromatogram after a first sample injection(30 minute run time per injection) upon system restart that illustrateda relatively large background of 184 μS at the end of run (see upperchromatogram of FIG. 4). Under an operating set-up (2 mm column, 29 mAcurrent, 0.3 ml/min flow rate, 38 mM KOH eluent, 2.5 ul loop size, 30°C.), the system continued to run for about 5 hours in order toequilibrate and achieve a CD background below 1 μS/cm (see lowerchromatogram of FIG. 4). The illustrated peaks are as follows: 1.Fluoride, 2. Acetate, 3. Chloride, 4. Carbonate, 5. Nitrite, 6. Sulfate,7. Bromide, 8. Nitrate, 9. Phosphate. The peak recovery of chloride wasnot optimal under these conditions, as compared to a no-down timecontrol since the suppressor capacity was depleted due to the largeconcentration of the eluent that traveled through the suppressor uponstartup.

Example 2

Table 1 displays a series of current and voltage settings for a reversebias configuration of a first eluent generator component. As illustratedin Table 1, a voltage of 2.1 V was applied (in the reverse biaspolarity—140 μA current was measured) that produced or resulted in thelowest conductivity—0.137 μS/cm—of the tested settings. This settinginhibited the transport of the species ions as evident from the lowbackground.

TABLE 1 Current (μA) Voltage (V) Conductivity (μS/cm) 0 28 2 0.5 2.80 60.8 1.70 35 1.8 0.226 64 1.95 0.172 81 2.04 0.147 140 2.1 0.137 270 2.430.142 312 2.90 0.143

Example 3

FIG. 5 illustrates measurements obtained under the normal operatingparameters of Example 1 after a 16 hour period of an applied reversebias passive mode polarity voltage of 2.1 V for the first eluentgenerator component. As depicted in FIG. 5 (upper chromatogram where nosample was injected), background conductivity reached 0.38 μS/cm afteronly 6 minutes following 16 hours of passive, reverse bias down time.Furthermore, peaks were substantially improved in shape and size,indicating a substantial increase in analyte recovery, as illustrated bythe subsequent chromatograms with two separate sample injections (seemiddle and lower chromatograms of FIG. 5). These surprising andunexpected results indicate that a reverse bias polarity voltage appliedduring a 16 hour passive mode or down times (e.g., with no aqueous fluidflow) provides a substantial reduction in startup, equilibration timeand a substantial improvement in analyte peaks area, indicating asubstantial increase in analyte recovery.

Example 4

Table 2 displays retention times and peak areas for common analytes fora no-down time control and 16 hour period of an applied reverse biaspassive mode polarity voltage of 2.1 V. As illustrated in Table 2,retention times and analyte peak areas an substantially similar for twoseparate injections following a 16 hour period of the applied reversebias passive mode polarity voltage of 2.1 V as for the no-down timecontrol.

TABLE 2 Injection after 16 hrs system shutdown (reverse bias 2.1 V)Control Injection #1 Injection #2 Ana- Retention Retention Retentionlyte Time Area Time Area Time Area F 2.56 0.4416 2.57 0.4446 2.5670.4411 Cl 5.197 1.2655 5.223 1.2199 5.2 1.2635 NO₂ 6.543 0.8831 6.5770.8719 6.54 0.88 SO₄ 7.947 0.9205 8.06 0.9188 7.957 0.9186 Br 12.8830.524  12.927 0.5274 12.853 0.5219 NO₃ 14.79 0.6784 14.833 0.676 14.7470.6767 PO₄ 19.027 0.7894 19.36 0.7787 19.03 0.7846

These surprising and unexpected results indicate that a reverse biaspolarity voltage applied during passive mode(s) or down times (e.g.,with no aqueous fluid flow) produces results similar results as constantoperation of the system without any down time. Overall these resultstranslate into productivity for the user since the instrument starts upwith no or minimal time lost.

Example 5

FIG. 6 illustrates measurements obtained under the normal operatingparameters of Example 1 after a 90 hour period of an applied reversebias passive mode polarity voltage of 2.1 V for the first eluentgenerator component. As depicted in FIG. 6, background conductivityreached 0.38 μS/cm after only 10 minutes following 90 hours of passive,reverse bias down time (upper chromatogram where no sample wasinjected). Furthermore, peaks were substantially improved in shape andsize, indicating a substantial increase in analyte recovery, asillustrated by the subsequent chromatograms with two separate sampleinjections (see middle and lower chromatograms of FIG. 6). Thesesurprising and unexpected results indicate that a reverse bias polarityvoltage applied during a 90 hour passive mode or down times (e.g., withno aqueous fluid flow) provides a substantial reduction in startup,equilibration time and a substantial improvement in analyte peaks area,indicating a substantial increase in analyte recovery.

Example 6

Table 3 displays retention times and peak areas for common analytes fora no-down time control and 90 hour period of an applied reverse biaspassive mode polarity voltage of 2.1 V for the first eluent generatorcomponent. As illustrated in Table 3, retention times and analyte peakareas an substantially similar for two separate injections following a90 hour period of the applied reverse bias passive mode polarity voltageof 2.1 V as for the no-down time control.

TABLE 3 Injection after 90 hrs system shutdown (reverse bias 2.1 V)Control Injection #1 Injection #2 Ana- Retention Retention Retentionlyte Time Area Time Area Time Area F 2.56 0.4399 2.573 0.4359 2.5630.4414 Cl 5.18 1.26  5.187 1.2502 5.183 1.2607 NO₂ 6.517 0.8817 6.520.8687 6.517 0.882 SO₄ 7.9 0.9109 7.853 0.8955 7.893 0.9122 Br 12.8070.5147 12.81 0.508 12.797 0.5173 NO₃ 14.693 0.6709 14.693 0.6727 14.6770.675 PO₄ 18.857 0.7892 18.81 0.7925 18.827 0.7903

These surprising and unexpected results indicate that a reverse biaspolarity voltage applied during passive mode(s) or down times (e.g.,with no aqueous fluid flow) produces results similar results as constantoperation of the system without any down time.

Example 7

Table 4 displays a series of current and voltage settings for a reversebias configuration of a second eluent generator component (a differentunit made in the same way as the first eluent generator component). Asillustrated in Table 4, a voltage of 2.35 V was applied (in the reversebias polarity—670 μA current was measured) that produced or resulted inthe lowest conductivity—0.17 μS/cm—of the tested settings.

TABLE 4 Current (μA) Voltage (V) Conductivity (μS/cm) 0 25 2 0.3 16.5 351.36 4.20 62 1.79 1.40 81 2.01 0.60 138 2.16 0.24 670 2.35 0.17 11702.53 0.18 1970 2.9 0.26

Example 8

FIG. 7 illustrates measurements obtained under the normal operatingparameters of Example 1 after a 16 hour period of an applied reversebias passive mode polarity voltage of 2.35 V for the second eluentgenerator component. As depicted in FIG. 7 (upper chromatogram where nosample was injected), background conductivity reached 0.36 μS/cm afteronly 7 minutes following 16 hours of passive, reverse bias down time.Furthermore, peaks were substantially improved in shape and size,indicating a substantial increase in analyte recovery, as illustrated bythe subsequent chromatograms with two separate sample injections (seemiddle and lower chromatograms of FIG. 7). These surprising andunexpected results indicate that a reverse bias polarity voltage appliedduring a 16 hour passive mode or down times (e.g., with no aqueous fluidflow) provides a substantial reduction in startup, equilibration timeand a substantial improvement in analyte peaks area, indicating asubstantial increase in analyte recovery.

Example 9

Table 5 displays retention times and peak areas for common analytes fora no-down time control and 16 hour period of an applied reverse biaspassive mode polarity voltage of 2.35 V for the second eluent generatorcomponent. As illustrated in Table 5, retention times and analyte peakareas are substantially similar for two separate injections following a16 hour period of the applied reverse bias passive mode polarity voltageof 2.35 V as for the no-down time control.

TABLE 5 Injection after 16 hrs system shutdown (reverse bias 2.35 V)Control Injection #1 Injection #2 Ana- Retention Retention Retentionlyte Time Area Time Area Time Area F 2.563 0.4389 2.567 0.4374 2.560.4395 Cl 5.19 1.2572 5.177 1.2496 5.18 1.2573 NO₂ 6.527 0.8791 6.510.8796 6.517 0.88 SO₄ 7.92 0.9086 7.863 0.9 7.903 0.9097 Br 12.8230.5149 12.803 0.5095 12.807 0.5152 NO₃ 14.713 0.6737 14.69 0.6662 14.6930.674 PO₄ 18.91 0.7824 18.813 0.7842 18.867 0.7834

These surprising and unexpected results indicate that a reverse biaspolarity voltage applied during passive mode(s) or down times (e.g.,with no aqueous fluid flow) produces results similar results as constantoperation of the system without any down time.

Example 10

Table 6 displays a series of current and voltage settings for a reversebias configuration of a third eluent generator component (a differentunit from the first and second eluent generator components, but made inthe same way). As illustrated in Table 6, a voltage of 2.24 V wasapplied (in the reverse bias polarity—136 μA current was measured) thatproduced or resulted in the lowest conductivity—0.144 μS/cm—of thetested settings.

TABLE 6 Current (μA) Voltage (V) Conductivity (μS/cm) 0 16 2 0.1 2.7 371.8 0.55 88 2.0 0.198 136 2.24 0.144 240 2.8 0.224 385 3.1 0.313

Example 11

FIG. 8 illustrates measurements obtained under the normal operatingparameters of Example 1 after a 16 hour period of an applied reversebias passive mode polarity voltage of 2.24 V for the third eluentgenerator component. As depicted in FIG. 8 (upper chromatogram where nosample was injected), background conductivity reached 0.36 μS/cm afteronly 7 minutes following 16 hours of passive, reverse bias down time.Furthermore, peaks were substantially improved in shape and size,indicating a substantial increase in analyte recovery, as illustrated bythe subsequent chromatograms with two separate sample injections (seemiddle and lower chromatograms of FIG. 8). These surprising andunexpected results indicate that a reverse bias polarity voltage appliedduring a 16 hour passive mode or down times (e.g., with no aqueous fluidflow) provides a substantial reduction in startup, equilibration timeand a substantial improvement in analyte peaks area, indicating asubstantial increase in analyte recovery.

Example 12

Table 7 displays retention times and peak areas for common analytes fora no-down time control and 16 hour period of an applied reverse biaspassive mode polarity voltage of 2.24 V for the third eluent generatorcomponent. As illustrated in Table 7, retention times and analyte peakareas an substantially similar for two separate injections following a16 hour period of the applied reverse bias passive mode polarity voltageof 2.24 V as for the no-down time control.

TABLE 7 Injection after 16 hrs system shutdown (reverse bias 2.24 V)Control Injection #1 Injection #2 Ana- Retention Retention Retentionlyte Time Area Time Area Time Area F 2.563 0.4306 2.573 0.4311 2.5670.4301 Cl 5.183 1.2437 5.233 1.2361 5.19 1.2401 NO₂ 6.52 0.8548 6.5870.8395 6.527 0.8521 SO₄ 7.913 0.8946 8.11 0.8891 7.947 0.8919 Br 12.8070.4997 12.94 0.4987 12.817 0.4974 NO₃ 14.69 0.6563 14.843 0.6543 14.70.6545 PO₄ 18.893 0.7587 19.457 0.7539 18.99 0.7566

These surprising and unexpected results indicate that a reverse biaspolarity voltage applied during passive mode(s) or down times (e.g.,with no aqueous fluid flow) produces results similar results as constantoperation of the system without any down time.

The present invention may be embodied in other specific forms withoutdeparting from its spirit or essential characteristics. The describedembodiments are to be considered in all respects only as illustrativeand not restrictive. The scope of the invention is, therefore, indicatedby the appended claims rather than by the foregoing description. Allchanges which come within the meaning and range of equivalency of theclaims are to be embraced within their scope.

The foregoing detailed description makes reference to specific exemplaryembodiments. However, it will be appreciated that various modificationsand changes can be made without departing from the scope contemplatedherein and as set forth in the appended claims. More specifically, whileillustrative exemplary embodiments in this disclosure have been moreparticularly described, the present disclosure is not limited to theseembodiments, but includes any and all embodiments having modifications,omissions, combinations (e.g., of aspects across various embodiments),adaptations and/or alterations as would be appreciated by those in theart based on the foregoing detailed description.

Alterations and further modifications of the inventive featuresillustrated herein, and additional applications of the principlesillustrated herein, which would occur to one skilled in the relevant artand having possession of this disclosure, are to be considered withinthe scope of this disclosure. Unless a feature is described as requiringanother feature in combination therewith, any feature herein may becombined with another feature of a same or different embodimentdisclosed herein. Furthermore, various well-known aspects ofillustrative systems, methods, apparatus, and the like are not describedherein in particular detail in order to avoid obscuring aspects of theexample embodiments.

The limitations in the claims are to be interpreted broadly based on thelanguage employed in the claims and not limited to examples described inthe foregoing detailed description, which examples are to be construedas non-exclusive. Moreover, any steps recited in any method or processdescribed herein and/or recited in the claims may be executed in anyorder and are not necessarily limited to the order presented in theclaims, unless otherwise stated (explicitly or implicitly) in theclaims. Accordingly, the scope of the invention should be determinedsolely by the appended claims and their legal equivalents, rather thanby the descriptions and examples given above.

It will also be appreciated that various features, members, elements,parts, and/or portions of certain embodiments of the present inventionare compatible with and/or can be combined with, included in, and/orincorporated into other embodiments of the present invention. Thus,disclosure of certain features, members, elements, parts, and/orportions relative to a specific embodiment of the present inventionshould not be construed as limiting application or inclusion of saidfeatures, members, elements, parts, and/or portions to the specificembodiment. Rather, it will be appreciated that other embodiments canalso include said features, members, elements, parts, and/or portionswithout necessarily departing from the scope of the present invention.Likewise, certain embodiments can include fewer features than thosedisclosed in specific examples without necessarily departing from thescope of this disclosure.

In addition, the present invention may be embodied in other specificforms without departing from its spirit or essential characteristics.The described embodiments are to be considered in all respects only asillustrative and not restrictive. The scope of the invention is,therefore, indicated by the appended claims rather than by the foregoingdescription. All changes which come within the meaning and range ofequivalency of the claims are to be embraced within their scope.

What is claimed is:
 1. A method of inhibiting translocation of an eluentthrough an ion exchange barrier of an ion exchange chromatographysystem, the method comprising: applying a voltage or current across afirst electrode and a second electrode, the voltage or current having afirst polarity, the first electrode being disposed on a first side ofthe ion exchange barrier, the second electrode being disposed on asecond side of the ion exchange barrier, the applied voltage or currentwith the first polarity electrolytically generating eluent ions at thesecond electrode and to generate a first electric field to promote thetranslocation of eluent counter ions through the ion exchange barrierfrom the first side to the second side, wherein the eluent counter ionsand the eluent ions combine to form the eluent; selectively reversing apolarity of the voltage or current from the first polarity to a secondpolarity to generate a second electric field that inhibits translocationof the eluent through the ion exchange barrier from the first side tothe second side; and selectively reversing the polarity of the voltageor current from the second polarity to the first polarity.
 2. The methodof claim 1, wherein the first electrode is in electrical communicationwith a liquid ion source disposed in an ion source reservoir, the firstelectrode is disposed in the ion source reservoir, the ion sourcereservoir is at the first side of the ion exchange barrier, the eluentcounter ions being disposed in the liquid ion source, the secondelectrode being in electrical communication with a liquid disposed in aneluent generation chamber, the second electrode is disposed in theeluent generation chamber, the eluent generation chamber is at thesecond side of the ion exchange barrier, the applied voltage or currentwith the first polarity generating the first electric field to promotethe translocation of the counter ions from the ion source reservoirthrough the ion exchange barrier toward the second electrode and to theeluent generation chamber, the applied voltage or current with thesecond polarity generating the second electric field to inhibit thetranslocation of the eluent towards the second electrode.
 3. The methodof claim 2, wherein the voltage or current having the first polaritycauses the first electrode to function as an anode and the secondelectrode to function as a cathode and the voltage or current having thesecond polarity causes the first electrode to function as a cathode andthe second electrode to function as an anode, wherein the ion exchangebarrier includes a cation exchange barrier.
 4. The method of claim 3,wherein the applied voltage or current with the first polarityelectrolytically generates hydronium ions at the first electrode andhydroxide at the second electrode.
 5. The method of claim 4, wherein theapplied voltage or current with the second polarity electrolyticallygenerates hydronium ions at the second electrode and hydroxide at thefirst electrode.
 6. The method of claim 2, wherein the voltage orcurrent having the first polarity causes the first electrode to functionas a cathode and the second electrode to function as an anode and thevoltage or current having the second polarity causes the first electrodeto function as an anode and the second electrode to function as acathode, wherein the ion exchange barrier includes an anion exchangebarrier.
 7. The method of claim 6, wherein the applied voltage orcurrent with the first polarity electrolytically generates hydroniumions at the second electrode and hydroxide at the first electrode. 8.The method of claim 7, wherein the applied voltage or current with thesecond polarity electrolytically generates hydronium ions at the firstelectrode and hydroxide at the second electrode.
 9. The method of claim1, wherein the ion exchange barrier substantially prevents liquid flowwhile providing an ion transport bridge.
 10. The method of claim 1,wherein inhibiting the translocation of the eluent through the ionexchange barrier from the first side to the second side inhibitsaccumulation of the eluent on the second side.
 11. The method of claim1, further comprising waiting a first period of time between the step ofselectively reversing the polarity of the voltage or current from thefirst polarity to the second polarity and the step of selectivelyreversing the polarity of the voltage or current from the secondpolarity to the first polarity.
 12. The method of claim 11, wherein thefirst period of time is greater than or equal to about 4 hours.
 13. Themethod of claim 11, further comprising initiating an automatic startupprocedure, the automatic startup procedure occurring over a secondperiod of time.
 14. The method of claim 13, further comprisinginitiating an equilibration procedure, the equilibration occurring overa third period of time.
 15. The method of claim 14, wherein the thirdperiod of time is less than or equal to about 60 minutes.
 16. The methodof claim 1, wherein the selectively reversing of the polarity of thevoltage or current from the first polarity to the second polarity occursduring a passive or shutdown mode.
 17. The method of claim 1, whereinthe second electric field inhibits translocation of the eluent counterions through the ion exchange barrier from the first side to the secondside.
 18. The method of claim 1 further comprising: after selectivelyreversing the polarity of the voltage or current from the secondpolarity to the first polarity, injecting analyte ions into the ionexchange chromatography system.
 19. The method of claim 1 furthercomprising: waiting an equilibration time period at the first polarityafter the selectively reversing the polarity of the voltage or currentfrom the second polarity to the first polarity, and then injectinganalyte ions into the ion exchange chromatography system.
 20. The methodof claim 19, wherein the equilibration time period is less than 15minutes.